Tuesday, 2 December 2008

Botox: If they only knew...

Humans are vain creatures. Perhaps only cats can tie humans on the vanity scale. And because we're so vain, we (or at least a select demographic) have become accustomed to poking, prodding, nipping, tucking, and injecting to make ourselves look younger and more beautiful. I'm talking, of course, about cosmetic surgery. It's reported that in the U.S alone, 11 million cosmetic surgeries were done in 2006. It's hardly a small industry.

But of all the different procedures which have become commonplace in the world of cosmetic augmentation, one has become particularly popular in the recent years: Botox.

Botox is a treatment used to get rid of unwanted wrinkles. Supposedly, it works well, because I doubt it would be so popular if it didn't. But there is one important fact about Botox that I don't believe many people who undergo the treatments ever ask themselves: what, exactly, is Botox?

To answer that, first we have to take a look at the lovely bacterium Clostridium botulinum (see the lovely image to the right), or rather what C. botulinumis best known for: it's toxin. If you or your parents or grandparents have ever made canned or jarred preserves, or if you have ever bought any from a farmer's market, then you are probably familiar with one big danger of eating such foods - botulism. If canned/jarred foods are not prepared correctly, you run the risk of contamination by C. botulinum. When ingested, the bacterium produce a toxin known as botulinum toxin, leading to botulism. Botulism is no simple food poisoning, either. Botulism is deadly. It causes a paralysis of the muscles and is very often deadly. It's so deadly that a 12oz glass of botulinum toxin is enough to kill every single person on the planet.

To understand the mechanism by which botulinum toxin (BTX) works, I should first explain a bit about how neurons work. When a signal is transferred from one neuron to another, it relies on the function of a neurotransmitter called acetlycholine (ACh). In general (and this is pretty general; I won't go into action potential polarization/depolarization), when an impulse travels down the axon of a neuron, it allows for ACh to be released across the synapse (the synapse is the space between the axon of one neuron and where it touches another). When the ACh reaches the surface of the next neuron, it binds to cellular receptors which signal to the neuron to continue the impulse, and the process continues from neuron to neuron. The whole process hinges on ACh being released and passed on to the next neuron down the line.

Inside of a neuron, ACh is stored in "synaptic vesicles". Think of them as little membrane-bound spheres that hold ACh until it's needed. In order for the ACh to go from inside the synaptic vesicle to the outside of the neuron, the vesicles bind and fuse to the axon membrane, releasing the ACh into the synapse. This process of binding and fusing is facilitated by two key proteins: synaptobrevin and SNAP-25. Synaptobrevin is a VAMP, or Vesicle-Associated Membrane Protein. In other words, Synaptobrevin sits on the outside of the synaptic vesicle. SNAP-25 sits on the cytoplasmic face of the axonal membrane. These two proteins interact with each other; synaptobrevin latches on to SNAP-25 to form what's known as a SNARE complex. The formation of this complex is what allows the synaptic vesicle to bind and fuse with the cellular membrane.

If all of that confused you, then let me put it in simpler terms. Synaptobrevin on the vesicle anchors onto SNAP-25 in the axon, allowing the vesicle to attach to the cellular membrane. The two fuse and ACh is released into the synapse. The nerve impulse is allowed to continue.

This is where botulinium toxin comes in. The BTX toxin is actually a protein consisting of two chains: the light chain and the heavy chain. The heavy chain is responsible for getting BTX into neurons; it binds to structures on the surface of the neuron, whereby it is internalized by endocytosis. Next, it's the light chain's turn to do it's dirty work. The light chain of the toxin actually works as a protease (that is, it cleaves proteins). The protein of choice of the light chain actually depends on the type of BTX toxin in question. BTX-A will cleave SNAP-25, whereas BTX-B will cleave synaptobrevin. Either way, the consequence should be obvious. With one of the components of the SNARE complex missing, the synaptic vesicles cannot bind and fuse, and ACh can no longer be released into the synapse.

This is bad news. With ACh being trapped inside of the neurons, neuronal impulses cannot be sent from one neuron to the next. This means that you can no longer send signals to your muscles telling them to relax or contract. You become completely paralyzed.

But what does all of this have to do with Botox, you ask? Well, Botox is simply a brand name for none other than botulinum toxin. It's actually botulinum toxin that cosmetic surgeons inject into your skin to make those wrinkles disappear. Wrinkles are caused by overactive muscles, and by injecting Botox, one can force them to relax and *poof*, no more wrinkles.

It is perfectly safe: the amount of toxin used is very small, and poses no significant health risks.Nevertheless, I can't help but think that the popularity of Botox treatments would be on the rapid decline if more people knew that they were actually injecting the world's most toxin protein into their faces.

2 comments:

My brother (with cerebral palsy) had botox injections to loosen the muscles in his legs. It's actually fairly common for that use too, which has more to do with a desire to walk (he didn't do enough physio so he still can't) and work muscles than vanity, but good article.

Botox is actually perscribed for a variety of medical reasons: originally it was used to simply stop uncontrollable muscle spasms, but has since been used to treat crossed eyes, excess sweating and migraines (though the evidence for that last one is disputed).